Lamivudine; Dolutegravir sodium for HIV infection

Inclusion criteria

• {"criterion_text":"- HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment\n- Aged 2 to <15 years old\n- Weight 6 kg or higher\n- Girls who have reached menarche must have a negative pregnancy test at screening and randomisation\n- Girls who are sexually active must be willing to adhere to highly effective methods of contraception\n- A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol\n- Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study"}

Exclusion criteria

• {"criterion_text":"- Any previous switch in ART regimen for virological, immunological or clinical treatment failure\n- Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)\n- Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)\n- Screening creatinine clearance <30 mL/min/1.73m2\n- Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)\n- Girls who are pregnant or breastfeeding\n- Children who are in the legal custody of the state and do not have a parent or guardian able to provide informed consent on their behalf\n- Evidence of previous resistance to 3TC or INSTI\n- Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for prevention of mother to child transmission\n- Known allergy or contraindications to dolutegravir or lamivudine\n- Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment\n- Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs (children can be enrolled after the illness resolves)\n- Randomisation visit more than 12 weeks after the most recent screening visit\n- Positive HBsAg\n- Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN AND bilirubin ≥2xULN)"}

Primary endpoints

• {"endpoint_text":"- Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 96.","definition_or_measurement_approach":"Confirmed viral rebound defined as the first of two consecutive HIV-1 RNA ≥50c/mL; assessed by HIV-1 RNA testing through week 96."}

Secondary endpoints

• {"endpoint_text":"- Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA ≥50c/mL) by week 48.","definition_or_measurement_approach":"Confirmed viral rebound defined as the first of two consecutive HIV-1 RNA ≥50c/mL; assessed by HIV-1 RNA testing at week 48."}
• {"endpoint_text":"- Proportion of children with confirmed HIV-1 RNA ≥50c/mL at weeks 48 and 96 (modified FDA snapshot)","definition_or_measurement_approach":"Modified FDA snapshot analysis of HIV-1 RNA ≥50c/mL at weeks 48 and 96 as specified in protocol."}
• {"endpoint_text":"- Proportion of children with HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures ≥50c/mL)","definition_or_measurement_approach":"Assessment of HIV-1 RNA ≥50c/mL at weeks 24, 48 and 96 including transient blips and confirmed measures."}
• {"endpoint_text":"- New resistance-associated mutations in those with confirmed HIV-1 RNA ≥50c/mL","definition_or_measurement_approach":"Genotypic resistance testing in participants with confirmed HIV-1 RNA ≥50c/mL."}
• {"endpoint_text":"- Time to any new or recurrent WHO 3 or WHO 4 event or death","definition_or_measurement_approach":"Time-to-event analysis for WHO stage 3/4 events or death as recorded during follow-up."}
• {"endpoint_text":"- Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96","definition_or_measurement_approach":"Laboratory measurement of absolute CD4 count and percentage at baseline and weeks 24, 48, 96."}
• {"endpoint_text":"- Incidence of serious adverse events, grade ≥3 clinical and laboratory adverse events","definition_or_measurement_approach":"Collection and grading of serious adverse events and grade ≥3 events per protocol definitions."}
• {"endpoint_text":"- Incidence of adverse events leading to discontinuation or modification of the treatment regimen","definition_or_measurement_approach":"Recording of AEs that cause treatment discontinuation or modification."}
• {"endpoint_text":"- Proportion of children with a change in ART for toxicity or switch to second-line","definition_or_measurement_approach":"Proportion analysis of participants changing ART due to toxicity or switching to second-line regimen."}
• {"endpoint_text":"- Change in blood lipids from baseline to weeks 48 and 96","definition_or_measurement_approach":"Laboratory measurement of blood lipid parameters at baseline, weeks 48 and 96."}
• {"endpoint_text":"- Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96","definition_or_measurement_approach":"Estimation of creatinine clearance using bedside-Schwartz formula at baseline and follow-up visits."}
• {"endpoint_text":"- Adherence as assessed by participant/care-giver questionnaires","definition_or_measurement_approach":"Questionnaire-based adherence assessments completed by participant or caregiver."}
• {"endpoint_text":"- Acceptability, sleep and mood, suicidality ideation and health-related quality of life as assessed by participant/care-giver completed questionnaires","definition_or_measurement_approach":"Participant/caregiver-completed questionnaires assessing acceptability, sleep, mood, suicidality ideation and HRQoL."}

Spain

Earliest CTIS Part Ii Submission Date

08-01-2025

Latest Decision Or Authorization Date

12-08-2025

Processing Time Days

216

Number Of Sites

2

Number Of Participants

6

Primary sponsor

Full Name

Fondazione Penta Ets

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Contract research organisations

Name

Almac Clinical Services Limited

Responsibilities

Sponsor duties (code 14); contact info info@almacgroup.com

Third parties

• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}